Prediction of Crohn's disease relapse with faecal calprotectin in infliximab responders: a prospective study.

BACKGROUND: Faecal calprotectin is a reliable tool for predicting Crohn's disease (CD) relapse in patients with sustained remission. Prediction of relapse with faecal calprotectin has been less studied in patients with severe CD treated with anti-TNF. AIM: To identify an association between faecal calprotectin concentration and CD clinical relapse in patients achieving remission with infliximab (IFX). METHODS: From February 2007 to October 2008, consecutive patients with refractory luminal CD were prospectively included when they received three IFX infusions (5mg/kg at weeks 0, 2 and 6) followed by maintenance with an immunomodulator alone. Faecal calprotectin and C-reactive protein (CRP) were measured at entry and at week 14 (w14). RESULTS: Sixty-five patients (43W; median age: 30.4years) were included, and 50 (77%) were in clinical remission off steroids at w14; twenty-three of fifty (46%) experienced CD clinical relapse during the first year of follow-up. Median faecal calprotectin level at w14 was similar in patients with and without CD clinical relapse (200 and 150µg/g respectively). When considering two suggested faecal calprotectin cut-offs to predict CD relapse, sensitivities and specificities were 61% and 48% for 130µg/g, respectively, and 43% and 57% for 250µg/g. Neither faecal calprotectin nor CRP at baseline and at w14 could predict relapse even when CD location subgroup analysis was considered. CONCLUSION: In patients responding to an infliximab induction regimen, faecal calprotectin measurement at w14 cannot predict Crohn's disease clinical relapse at 1year.

The tolerance and efficacy of a postponed retreatment with infliximab in Crohn's disease primary responders.

BACKGROUND: In Crohn's disease (CD) patients naïve to immunomodulators primary responding to infliximab (IFX) induction, maintenance with scheduled IFX or with immunomodulators is possible. The benefit of additional IFX infusions after failure of maintenance with immunomodulators is not known. AIM: To assess the efficacy and factors associated with efficacy of postponed IFX retreatment. METHODS: All CD primary responders to an IFX induction regimen in maintenance with immunomodulators were retrospectively included when they received at least one additional IFX infusion after week 14. Efficacy was defined as clinical response at week 4 and absence of intolerance leading to discontinuation. RESULTS: Sixty-one patients were retreated with IFX with a 38-week median time from induction. Efficacy was achieved in 80% patients. Twelve patients had no clinical benefit: seven acute hypersensitivity reactions and five loss of response. By multivariate analysis, the only factor associated with no efficacy was a median time >50 weeks from induction to retreatment (odds ratio = 7.38; 95%CI: 1.38-39.59; P = 0.02). CONCLUSION: Postponed retreatment with IFX in CD primary responders should be administered within 50 weeks after induction, for better efficacy and tolerance.

Changes of non-invasive markers and FibroScan values during HCV treatment.

The recent advent of non-invasive methods for assessment of fibrosis allows serial assessments in all patients with hepatitis C. The aim of this prospective study was to evaluate changes in liver fibrosis, as measured with non-invasive methods, in a large cohort of HCV-infected patients with and without treatment. From May 2003 through March 2006, all previously untreated HCV-infected patients were enrolled in this study. Liver fibrosis was staged with FibroScan and Fibrotest at inclusion, then every year in untreated patients, and at the end of treatment and 6 months later in treated patients. The study population consisted of 416 patients, of whom 112 started treatment after enrolment. In the treatment group, FibroScan and Fibrotest values were significantly higher before and after treatment than in untreated patients at baseline and after 1 year. However, there was no significant difference between treated and untreated patients at the end of follow-up. FibroScan and Fibrotest values fell in all treated patients, whatever their virological response. In multivariate analysis, treatment was the only factor independently associated with a fall in the FibroScan value. In conclusion, whatever the virological response, treatment for HCV infection is associated with an improvement of FibroScan and Fibrotest values. Further studies are needed to compare these non-invasive methods with liver biopsy. These non-invasive methods, and especially FibroScan, should be useful for assessing treatment efficacy in clinical trials of new drugs.

[The liver and methotrexate]. / Foie et méthotrexate.

Methotrexate is proposed for the treatment of inflammatory disorders such as rheumatoid arthritis, psoriasis and Crohn's disease. The liver toxicity of methotrexate has been investigated and prolonged treatment can induce liver fibrosis. Moreover, alcohol consumption, diabetes and obesity are associated with liver fibrosis in patients treated with this drug. Therefore, liver fibrosis associated with methotrexate could be due to associated factors instead of methotrexate itself. Recommendations to monitor and diagnose methotrexate induced liver damage vary depending on the disease. Frequent evaluation of liver fibrosis with liver biopsy is recommended during therapy, especially in patients treated for psoriasis. Noninvasive methods, such as the FibroScan, could be useful for the assessment of liver fibrosis associated with methotrexate and hence, need further evaluation.

Diagnosis of liver fibrosis using FibroScan and other noninvasive methods in patients with hemochromatosis: a prospective study.

BACKGROUND: The role of hepatic iron overload in the development of hepatic fibrosis in patients with hemochromatosis is well-established. Transient elastography (FibroScan) is a new noninvasive, rapid, reproducible bedside method, allowing assessment of liver fibrosis by measuring liver rigidity. OBJECTIVES: The aim of this prospective study was to evaluate liver fibrosis with FibroScan and other noninvasive biochemical methods in patients with hemochromatosis (C282Y homozygosity) compared with control patients. PATIENTS AND METHODS: From January 2004 through October 2006, all consecutive patients with hemochromatosis were evaluated for liver fibrosis using noninvasive methods (FibroScan and biochemical markers). These patients were compared with patients who had chronic cytolysis and no fibrosis on liver biopsy. RESULTS: One hundred and three consecutive patients (57 cases and 46 controls) were fully investigated. Median FibroScan values were similar in both groups, 5.20 kPa versus 4.9 kPa, respectively. No differences were observed between cases and controls for all biochemical markers. A strong correlation was observed between FibroScan and many biochemical markers, although ferritin levels did not correlate with FibroScan values. The prevalence of patients with FibroScan values greater than 7.1 kPa (cut-off level for significant fibrosis) was 22.8% in patients with hemochromatosis and 0% in the controls (P<0.0001). CONCLUSION: FibroScan and biochemical markers could be reliable noninvasive methods for detecting liver fibrosis in patients with hemochromatosis. Such patients have high FibroScan values more often than do control patients. Further longitudinal and prospective studies are necessary to confirm these preliminary data.

Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study.

BACKGROUND: Transient elastography (FibroScan) is a new, non-invasive, rapid, and reproducible method allowing evaluation of liver fibrosis by measurement of liver stiffness. In cirrhotic patients, liver stiffness measurements range from 12.5 to 75.5 kPa. However, the clinical relevance of these values is unknown. The aim of this prospective study was to evaluate the accuracy of liver stiffness measurement for the detection of cirrhosis in patients with chronic liver disease. METHODS: A total of 711 patients with chronic liver disease were studied. Aetiologies of chronic liver diseases were hepatitis C virus or hepatitis B virus infection, alcohol, non-alcoholic steatohepatitis, other, or a combination of the above aetiologies. Liver fibrosis was evaluated according to the METAVIR score. RESULTS: Stiffness was significantly correlated with fibrosis stage (r=0.73, p<0.0001). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.80 (0.75-0.84) for patients with significant fibrosis (F>2), 0.90 (0.86-0.93) for patients with severe fibrosis (F3), and 0.96 (0.94-0.98) for patients with cirrhosis. Using a cut off value of 17.6 kPa, patients with cirrhosis were detected with a positive predictive value and a negative predictive value (NPV) of 90%. Liver stiffness was significantly correlated with clinical, biological, and morphological parameters of liver disease. With an NPV>90%, the cut off values for the presence of oesophageal varices stage 2/3, cirrhosis Child-Pugh B or C, past history of ascites, hepatocellular carcinoma, and oesophageal bleeding were 27.5, 37.5, 49.1, 53.7, and 62.7 kPa, respectively. CONCLUSION: Transient elastography is a promising non-invasive method for detection of cirrhosis in patients with chronic liver disease. Its use for the follow up and management of these patients could be of great interest and should be evaluated further.